Abnormal neuroleptic/dopamine receptors in schizophrenia.

In order to test the dopamine hypothesis of schizophrenia, the neuroleptic/dopamine receptors in three dopamine-rich regions of 53 postmortem normal human brains and 42 schizophrenic brains were measured using 3H-haloperidol and 3H-spiperone. The binding of 2 nM 3H-haloperidol was significantly elevated in the caudate nucleus (90 +/- 10%) and the putamen (61 +/- 6%) from schizophrenic brains. The binding of 1 nM 3H-spiperone was also elevated by 50 +/- 7% in schizophrenic caudate and 47 +/- 8% in the putamen. The nucleus accumbens from schizophrenic brains revealed an enhanced binding of 110 to 115%. In those schizophrenic patients who had no history of being treated with neuroleptic drugs the brain regions also exhibited significantly higher (29-80%) binding of 3H-neuroleptics. The results are compatible with the hypothesis that schizophrenia may be associated with an overactivity of postsynaptic dopamine receptors.